The overall objective of research supported by this grant is to characterize the effects of metabolic, pharmacologic, and mechanical stimuli on the activity of cardiac receptors with nonmyelinated vagal afferents and to determine whether these stimuli can significantly alter the inhibition of the vasomotor center exerted by these cardiac receptors. The discharge of these receptors will be studied in an in situ preparation in which the mechanical stimulus to the receptor can be controlled. It has been suggested by J.C.G. Coleridge and colleagues that cardiac mechanoreceptors with nonmedullated vagal afferents do not respond to a variety of naturally occurring substances such as prostaglandins and bradykinin whereas other cardiac C-fibers which are not mechanically activated are activated by these substances. I plan to re-examine this issue under circumstances where the stimulus to the receptor can be controlled and the drug can be injected directly into the solution perfusing the coronary arteries. The second goal of the ccming year is to continue studies of the reflex effects mediated through cardiopulmonary receptors with vagal afferents. As we begin to investigate the influence of substances such as prostaglandins and bradykinin on the discharge of these receptors, we also plan to investigate the reflex mechanisms mediated through these receptors in response to alterations in the local synthesis of these substances (e.g. as may occur during myocardial ischemia).